Pharmacokinetics of clonidine and chlorthalidone following subacute administration of a fixed combination compared with a sustained release formulation of clonidine alone
Arndts, D.; Doevendans, J.; Arendt, G.; Rippen, G.
Arzneimittel-Forschung 31(11): 1954-1957
1981
ISSN/ISBN: 0004-4172 PMID: 7198476 Document Number: 173707
Clonidine concentrations in urines and blood plasma samples analysed by RIA were observed over a period of 240 h in 6 male, healthy, normotensive volunteers being treated for 7 days with sustained-release formulations of 2-(2,6-dichloroanilino)-2-imidazoline (clonidine, Catapresan) alone (0.15 mg/d) and subsequently with a combination containing 0.15 mg clonidine plus 15 mg chlorthalidone. Chlorthalidone was determined in blood samples using a newly developed massfragmentographic method. The trials revealed: 1. There is no influence of chlorthalidone on the pharmacokinetics of clonidine. 2. the steady-state levels of the plasma or blood concentrations being reached on the 2nd (clonidine) and on the 5th day (chlorthalidone) were adjusted subsequently in therapeutically relevant ranges ranging between minima and maxima of 0.2 and 0.6 ng/ml (clonidine) and between 2.4 and 2.6 microgram/ml (chlorthalidone) respectively. From pharmacokinetic aspects therefore a fixed combination of two synergistic antihypertensive agents can be considered as useful. 3. Following 7 administrations of either clonidine formulation 63% of the total clonidine doses were excreted renally.